Bivalent rotavirus VP4∗ stimulates protective antibodies against common genotypes of human rotaviruses

Non-replicating rotavirus vaccines are an alternative strategy to improve the efficacy and safety of rotavirus vaccines. The spike protein VP4, which could be enzymatically cleaved into VP8∗ and VP5∗, is an ideal target for the development of recombinant rotavirus vaccine. In our previous studies, we demonstrated that the truncated VP4 (aa26-476, VP4∗) could be a more viable vaccine candidate compared to VP8∗ and VP5∗. Here, to develop a human rotavirus vaccine, the VP4∗ proteins of P[4], P[6], and P[8] genotype rotaviruses were expressed. All VP4∗ proteins can stimulate high levels of neutralizing antibodies in both guinea pigs and rabbits when formulated in aluminum adjuvant. Furthermore, bivalent VP4∗-based vaccine (P[8] + P[6]-VP4∗) can stimulate high levels of neutralizing antibodies against various genotypes of rotavirus with no significant difference as compared to the trivalent vaccines. Therefore, bivalent VP4∗ has the potential to be a viable rotavirus vaccine candidate for further development.